Nausea and vomiting are distressing symptoms associated with a variety of conditions such as motion sickness, pain, and a number of gastrointestinal disorders. Emesis also occurs in a number of clinical situations such as following cancer chemotherapy and surgery under general anaesthesia. The impact of these symptoms on the quality of life of sufferers is severe, so much so in the case of cancer chemotherapy as to have a significant impact on compliance.
Although the emergence of 5-HT.sub.3 receptor antagonists has had an impact on the treatment of emesis induced by anti-cancer therapy, their major effects are confined to the acute phase of the response. Anti-cancer drugs induce acute emesis via actions in the gut, specifically the release of 5-HT which activates receptors on abdominal vagal afferents. This is wholly consistent with the observations that 5-HT.sub.3 antagonists have a relatively restricted anti-emetic profile. Thus, these compounds are less effective against the delayed emesis observed following cancer chemotherapy, post-operative emesis, muscarinic receptor agonists, and erythromycin.
NK.sub.1 receptor antagonists have been shown to possess a broad anti-emetic spectrum, have a different site of action, and provide the best opportunity to date of an antiemetic therapy which will be effective against a wide range of emetogenic compounds and conditions, U.S. Pat. No. 5,360,820.
Treatment of emesis is intended to include prophylaxis as well as the alleviation of established symptoms.
The treatment of emesis includes the treatment of nausea, retching, and vomiting. Emesis includes acute emesis, delayed emesis, and anticipatory emesis. For example, emesis may be induced by drugs such as cancer chemotherapeutic agents such as alkylating agents, e.g. cyclophosphamide, carmustine, lomustine, and chlorambucil; cytotoxic antibiotics, e.g. dactinomycin, doxorubicin, mitomycin-C, and bleomycin; antimetabolites, e.g. cytarabine, methotrexate, and 5-fluorouracil; vinca alkaloids, e.g. etoposide, vinblastine, and vincristine; and others such as cisplatin, dacarbazine, procarbazine, and hydroxyurea; and combinations thereof; radiation sickness; radiation therapy, e.g. irradiation of the thorax or abdomen, such as in the treatment of cancer; poisons; toxins, such as toxins caused by metabolic disorders or by infection, e.g. gastritis; pregnancy; vestibular disorders, such as motion sickness; post-operative sickness; gastrointestinal obstruction; reduced gastrointestinal motility; visceral pain, e.g. myocardial infarction or peritonitis; migraine; increased intercranial pressure; decreased intercranial pressure (e.g. altitude sickness); and opioid analgesics, such as morphine.